Investigations in this program are carrying out studies which will characterize vascular changes in hypertension and give insight into the mechanisms responsible for these changes. Our primary experimental model is the pig made hypertensive by mineralocorticoid, electrolyte, or renal interventions. Rats, rabbits, and humans are also used. Our overall strategy has called for an attack on the problem at two levels: 1) Structural and functional changes in blood vessels are being characterized during the development of elevated arterial pressure. Observations range from those defining subcellular structure and function of vascular smooth muscle and endothelium to those dealing with whole-body vascular reactivity, autoregulation, and compliance. 2) In order to give insight into the mechanisms responsible for the vascular changes, observations are being made of the sequence of events beginning with the particular experimental intervention and ending with the vascular changes responsible for the elevated arterial pressure. Studies in this area include measurements of hemodynamic changes, water and electrolyte balance, and endocrine levels (renin, aldosterone, desoxycorticosterone, prostaglandins, and kallikrein). We are currently learning about the mechanisms responsible for the changes that we have observed with mineralocorticoid hypertension by attempting to alter the changes with specific interventions such as renal denervation, indomethacin or vasopressin administration, low or high sodium diets, etc.